I like this little piece because it shows a history of our disorder from 1955 that remained constant and if you read the old articles the descriptions match what is know today. The question is: How was this ignored for so long? In 1969 we knew almost all of the characterization of HPPD.

Changes in receptor density was the conclusion I came to a year and a half to two years ago when I was doing nothing but reading reading and reading more about the subject non-stop. It seems as if the generation of receptor proteins during or after a significant drug session to cause enough change in the visual cortex to be semi-permanent to permanent makes the most sense out of anything else. The other idea I dwelled on was cell death, but that doesn't make much sense to me. If a consumed drug was powerful enough to cause apoptosis then I don't believe it would be confined to one specific area of the brain.

Plus if a large amount of cells die--like would be the case with hppd--either through apoptosis or necrosis, it would make sense that there would be inflamation or leasons, which are detectable by a mri.

While changes in receptor density is totally undectable on a standard mri.

This is another thing I never understood. I have read that neurotransmitter depletion is something that is slowly fixed as certain amines reach our brains. But what about their receptors? When a receptor is damaged, how is it fixed? Is our brain continuously making new receptors?

I have seen an animation showing how a strange molecule that is similar to a neurotransmitter will bind to a receptor as if it were the neurotransmitter, but leaving a kind of damage because of it's different structure. If that is true I wonder why nobody talks about this effect when the subject is HPPD, because looking at the structure of LSD, it is really similar to serotonin.

In time, if the problem is actually a change in receptors density, aren't there lots of methods available to up regulate a group of receptors?

1) Cellular death would be detectable only if the neuronal damage large enough scale. However, this is unlikely because 1) not dose dependent to severity correlational, let alone causal relationship, 2) delayed onset post-precipitant event when assumed to be hallucinogen related.

2) Regarding the depletion of neurotransmitters: I cover this in my Neurobiology section, but here is the very short version: Depletion can occur via multiple mechanisms. Including agonism at the receptor resulting in depolarization of the cell and release of transmitters in the cell and receptor density lowering immediately. Receptors are replaced and damage to a receptor would persist only if the genes encoding for the receptor were altered, a specific sub-unit of a receptor is improperly coded, or the early immediate-early gene like c-fos. If HPPD individuals were particularly sensitive to returning to normal gene expression after experiencing changes then you have one possible explanation. The neuron is not making receptors at the same rate because of long-term potentiation for example. In the case of benzo use, the GABA receptor will down-regulate. It takes a long time for the cells to process and eventually return to the normal rate to generate the receptor complexes.

3) LSD is great at binding to specific 5-HT receptors. If LSD were to cause a conformational (structural) change in a receptor, it would happen to all users of LSD. Unless, the HPPD individual has a receptor complex that is just enough "off" in structure to be suceptible to this alteration in structure (for example, some chemicals will actually get stuck and block the receptor, I think picrotoxin operates this way. However, the affect would be dose dependent and we would look for problems with other serotonin agonists (including serotonin itself). LSD also is rare in that it has Dopaminergic action as well.

I'll try to get this out as soon as possible. Do know that 5-HT receptor density in blood platelets is one way to measure what is happening in the brain.